PROJECT SUMMARY The ongoing nation-wide opioid crisis incurs devastating consequences not only for those who abuse drugs themselves but also for fetuses exposed to opioids during pregnancy2-4. Drug use during pregnancy, both licit/prescription drugs and illicit substances, is on the rise7. Significant adverse developmental outcomes in prenatally-exposed children are documented beyond perinatal abnormalities9-11. However, drug-specific long-term effects remain poorly understood and little is known about potential risk and resilience factors that may exacerbate or mitigate their effects4. The current Healthy Brain and Child Development (HBCD) RFA represents an urgently needed and highly important effort to tackle this critical research gap. In 2016, California had 4654 drug overdose deaths, the 2nd highest number in the nation15. The prevalence rate of opioids misuse in the Los Angeles county (LA) in 2017 is 4.8%, higher than the national average of 4.5%, and is still on the rise15. Prevalence rates are particularly high among individuals of childbearing age, and in already-vulnerable populations including African American females15,21. Together, these data highlight a pressing need for a systematic study of the effects of prenatal drug exposures (PDE) in the unique sociodemographic LA county area. Our team has extensive experience in longitudinal neuroimaging8,22-25 and behavioral study13,19,20,26-30 of both normal5,8,12,19,25,26,31,32 and at-risk infants/children2,3,14,18,33 with different prenatal drug exposures. In this project, we aim to leverage these experiences and establish the feasibility for the large-scale Phase II HEALthy BCD study in the Los Angeles area with three specific aims: (1). To build a broad interdisciplinary team of investigators capable of a multi-faceted study of brain and behavioral development in both typically developing and at-risk infants/children; (2). To establish a set of highly executable recruitment and retention strategies for both drug-free and drug-exposed infants/children; and (3). To establish comprehensive study protocols that will help address the three key research objectives of the Phase II study. This project is significant because it is expected to prepare our LA team and sites to be ready to participate in the nation-wide HEALthy BCD study so that the at-risk pregnant women and children in the unique sociodemographic LA area can be represented and potentially benefit from this important study. It is innovative because: 1) our distributed network of recruitment sites covering divergent populations including both privileged and resource-deprived families will provide a unique opportunity to study socioeconomic-related risk and resilience factors on PDE; and 2) our experienced team will develop innovative recruitment/retention strategies and study protocols to better prepare for the Phase II HEALthy BCD study. It is relevant to public health because it represents the start to better understand and potentially address one of the most devastating problems affecting our next generation-prenatal drug exposure in one of the nation?s most populated and most affected areas-the Los Angeles County area.